Of particular interest is the descending control system that regulates transmission of nociceptive information. This system presumably suppresses excessive pain under certain circumstances. For example, it is well known that soldiers on the battlefield, accident victims, and athletes in competition often feel little or no pain at the time a wound occurs or a bone is broken. At a later time, pain may develop and become severe. Although the descending regulatory system that controls pain is part of a more general centrifugal control system that modulates all forms of sensation, the pain control system is so important medically that it is distinguished as a special system called the endogenous analgesia system.
Several centers in the brainstem and pathways descending from these centers contribute to the endogenous analgesia system. For example, stimulation in the midbrain •Fig. 7.9 A, Modelsofdescendingcontrolofascendingpainpathways.A,Schematicshowingtheascendingnociceptivepathwaythatconveyspaininformationtothebrain,representedbythespinothalamictract(STT),andthedescendingpathwaythatmodulates(gates)theflowofinformationintoit.Thedescendingpathwaystartsintheperiaqueductalgray(PAG),whichprojectsviatherostroventromedial(RVM)medullatothedorsalhorn.ActivationofthePAGorRVMblockstransmissionofpaininformationatthespinalcordlevel.B,Thestandardmodelofdescendingcontrolofpainperception.TonicallyactiveGABAergicinterneuronsinthePAGandRVMinhibittheprojectioncells(notethatthePAGhaslocalGABAergicinterneuronsbutalsoreceivesGABAergicterminalsfromotherbrainregions,andbothmaybeinvolvedintonicallyinhibitingthePAGprojectioncells).OpioidsappeartoinhibittheGABAergicinterneurons,thusdisinhibitingtheprojectionneurons,whoseincreasedactivityleadstoblockingtheactivationofSTTcellsbynociceptivedorsalrootganglion(DRG)cells.C,Parallelinhibition-excitationmodel.SomestudiessuggestbothexcitatoryandinhibitorycellsprojectfromthePAGandtheRVM.Inthismodel,gatingoftransmissionofpaininformationwouldbeduetoabalanceoftheexcitatoryandinhibitoryactivityinthedescendingpathways.Notethattheexcitatoryandinhibitorypathwaysareshownonoppositesidesjustforclarity.D,Possiblepresynapticandpostsynapticsitesofactionofenkephalin(Enk).ManyoftheterminalsfromthedescendingpathwaysforpainmodulationreleasebothGABAandenkephalin(EnK),whichappearstohavebothpre-andpostsynapticsitesofaction.ThepresynapticactionmightpreventreleaseofsubstanceP(SubP.)fromnociceptors.(A-C,RedrawnfromLauBK,VaughanCW.Curr Opin Neurobiol 2014;29:159.D,RedrawnfromHenryJL.In:PorterR,O’ConnorM[eds]:CibaFoundationSymposium91.London:Pitman;1982.) periaqueductal gray, locus coeruleus, or medullary raphe nuclei inhibits nociceptive neurons at the spinal cord and brainstem level, including spinothalamic and trigeminothalamic tract cells (
Fig. 7.9A-C ). Other inhibitory pathways originate in the sensorimotor cortex, hypothalamus, and reticular formation.
The endogenous analgesia system can be subdivided into two components: one component uses endogenous opioid peptides as neurotransmitters and the other does not. Endogenous opioids are neuropeptides that activate one of several types of opiate receptors. Some of the endogenous